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Background Mental disorders, one of the leading causes of the global health-related burden, which has been exacerbated by the emergence of the COVID-19 pandemic (2019–2021). In this study, we aim to provide global, regional, and national estimates of the mental disorders burden from 1990 to 2021, including during the COVID-19. Methods We collected data from the Global Burden of Disease Study 2021 (GBD 2021) on the incidence, disability-adjusted life years (DALYs), age-standardized incidence rate (ASIR), and age-standardized DALY rate (ASR) of 12 mental disorders from 204 countries and regions. The socio-demographic index (SDI) was used to evaluate the correlation between mental disorders burden and different regions. We utilized joinpoint regression analysis to estimate the average annual percentage change (AAPC). Results In 2021, there were 444,397,716 incident cases and 155,418,119 DALYs globally from mental disorders. From 1990 to 2021, there was an upward trend in both ASIR [15.23% (12.97–17.60%)] and ASR [17.28% (15.06–19.44%)]. In 2021, the highest ASIR was observed in Central Sub-Saharan Africa (8706.11), while the lowest was in East Asia (3340.99). Australia (2787.87) had the highest ASR. Nationally, Greenland, Greece, the United States, and Australia had the highest ASRs. During the COVID-19 pandemic, aside from East Asia, both the ASIR showed an upward trend in the five SDI and other GBD regions. In 2021, the ASR for females was higher than that for males. Among the 12 subtypes, major depressive disorder (557.87) and anxiety disorders (524.33) had the highest ASR. Major depressive disorder ranked first in ASR in 13 of the 21 regions worldwide. Despite the overall upward trend in DALYs for mental disorders [AAPC: 5.96; 95%CI: (4.99, 6.92)], the ASR exhibited varying trends among different subtypes, with anxiety disorders experiencing the most significant increase. Conclusions GBD 2021 showed that the burden of mental disorders has increased over the past three decades, with notable regional disparities. High SDI regions and females should be paid more attention. To alleviate future burdens, providing comprehensive mental health support, establishing effective mental health knowledge dissemination and tailored interventions are in great need. Clinical trial number Not applicable.

Following dramatic success in many types of advanced solid tumors, interest in immunotherapy for the treatment of colorectal cancer (CRC) is increasingly growing. Given the compelling long-term durable remission, two programmed cell death 1 (PD-1)-blocking antibodies, pembrolizumab and nivolumab (with or without Ipilimumab), have been approved for the treatment of patients with metastatic colorectal cancer (mCRC) that is mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H). Practice-changing results of several randomized controlled trials to move immunotherapy into the first-line treatment for MSI-H metastasis cancer and earlier stage were reported successively in the past 2 years. Besides, new intriguing advances to expand the efficacy of immunotherapy to mCRC that is mismatch-repair-proficient and low microsatellite instability (pMMR-MSI-L) demonstrated the potential benefits for the vast majority of mCRC cases. Great attention is also paid to the advances in cancer vaccines and adoptive cell therapy (ACT). In this review, we summarize the above progresses, and also highlight the current predictive biomarkers of responsiveness in immunotherapy with broad clinical utility.

Medicine has encountered unprecedented problems associated with changes in nature, society, and environment, as well as with new human quests for survival, longevity, and health. In the meantime, the development of medicine is facing challenges that resulted from the over-division and specialization of disciplines and the fragmentation of medical knowledge. To construct a new medical system that is more suitable for human health and disease treatment, holistic integrative medicine (HIM), which regards the human body as a holistic entity, organically integrates the most advanced knowledge and theories in each medical field and the most effective practices in various clinical specialties to revise and adjust on the basis of social, environmental, and psychological conditions. HIM is the inevitable and necessary direction for the future development of medicine. In this article, we illustrated the connotation of HIM, the differences between HIM and other medical conceptions, and the practice of HIM in recent years.

Background The diagnostic and prognostic significance of carcinoembryonic antigen (CEA), carbohydrate associated antigen 19–9 (CA19–9), alpha-fetoprotein (AFP) and cancer antigen 125 (CA125) in early gastric cancer have not been investigated yet. Thus, the present study aimed to explore the diagnostic and prognostic significance of the four tumor markers for early gastric cancer. Methods From September 2008 to March 2015, 587 early gastric cancer patients were given radical gastrectomy in our center. The clinicopathological characteristics were recorded. The association between levels of CEA and CA19–9 and clinicopathological characteristics and prognosis of patients were analyzed. Results There were 444 men (75.6%) and 143 women (24.4%). The median age was 57 years (ranged 21–85). The 1-, 3- and 5-year overall survival rate was 99.1%, 96.8% and 93.1%, respectively. The positive rate of CEA, CA19–9, AFP and CA125 was 4.3%, 4.8%, 1.5% and 1.9%, respectively. The positive rate of all markers combined was 10.4%. The associations between the clinicopathological features and levels of CEA and CA19–9 were analyzed. No significant association was found between CEA level and clinicopathological features. However, elevated CA19–9 level was correlated with female gender and presence of lymph node metastasis. Age > 60 years old, presence of lymph node metastasis and elevation of CEA level were independent risk factors for poor prognosis of early gastric cancer. Conclusions The positive rates of CEA, CA19–9, APF and CA125 were relatively low for early gastric cancer. Elevation of CA19–9 level was associated with female gender and presence of lymph node metastasis. Elevation of CEA level was an independent risk factor for the poor prognosis of early gastric cancer.

Berberine, an isoquinoline alkaloid isolated from the Chinese herb Coptis chinensis and other Berberis plants, has a wide range of pharmacological properties. Berberine can be used to treat many diseases, such as cancer and digestive, metabolic, cardiovascular, and neurological diseases. Berberine has protective capacities in digestive diseases. It can inhibit toxins and bacteria, including Helicobacter pylori, protect the intestinal epithelial barrier from injury, and ameliorate liver injury. Berberine also inhibits the proliferation of various types of cancer cells and impedes invasion and metastasis. Recent evidence has confirmed that berberine improves the efficacy and safety of chemoradiotherapies. In addition, berberine regulates glycometabolism and lipid metabolism, improves energy expenditure, reduces body weight, and alleviates nonalcoholic fatty liver disease. Berberine also improves cardiovascular hemodynamics, suppresses ischemic arrhythmias, attenuates the development of atherosclerosis, and reduces hypertension. Berberine shows potent neuroprotective effects, including antioxidative, antiapoptotic, and anti-ischemic. Furthermore, berberine exerts protective effects against other diseases. The mechanisms of its functions have been extensively explored, but much remains to be clarified. This article summarizes the main pharmacological actions of berberine and its mechanisms in cancer and digestive, metabolic, cardiovascular, and neurological diseases.

Background and objective Gastric cancer (GC) remains a significant global health challenge, characterized by high incidence and mortality rates, particularly in East Asia. A comprehensive understanding of the disease burden of gastric cancer is crucial for developing effective prevention and treatment strategies. However, comprehensive global assessments of the disease burden of gastric cancer remain limited. This study, based on the Global Burden of Disease (GBD) framework, systematically analyzes global trends in gastric cancer from 1990 to 2021 and projects future trends through 2035, aiming to provide scientific evidence for policymaking. Methods The data were derived from the Global Burden of Disease (GBD) Study 2021, covering gastric cancer (GC) incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs), and age-standardized DALY rates (ASRs) across 204 countries and regions from 1990 to 2021. The Bayesian age-period-cohort model was employed to project trends up to 2035. Results In comparison with 1990, both the incidence and mortality of GC rose in 2021, with over 1.23 million new cases recorded globally, resulting in 954,373.60 deaths and 22,786,633.10 DALYs. Between 1990 and 2021, the ASIRs, ASDRs, and ASRs decreased by 42% (ranging from 49 to 35%), 49% (ranging from 55 to 43%), and 53% (ranging from 58 to 47%), respectively. The peak ASIRs and ASDRs in 2021 were seen in the high-middle SDI quintile. Males exhibited higher rates of ASDRs, ASIRs, and ASRs compared to females. In 2021, East Asia and high-income North America bore the largest burden of smoking-related GC, while Central Europe experienced the highest burden from high-sodium diets. Forecasts toward 2035 indicate a continued decline in both ASIRs and ASDRs. Conclusions Despite notable reductions in both incidence and mortality, GC remains a substantial global burden, affecting various regions and countries. Deaths and DALYs related to high-sodium diets and smoking have shown an overall decline. However, substantial regional and age-related disparities persist. Targeted interventions, such as smoking control and promoting the intake of fresh fruits and vegetables, are essential in diminishing GC risk.

The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n  = 390; cohort II, n  = 363) and found that SOX12 was significantly upregulated in CRC, indicating a poor prognosis in CRC patients. Overexpression of SOX12 promoted CRC cell proliferation and metastasis, whereas downregulation of SOX12 hampered CRC aggressiveness. Mechanistically, SOX12 facilitated asparagine synthesis by transactivating glutaminase ( GLS ), glutamic oxaloacetic transaminase 2 ( GOT2 ), and asparagine synthetase ( ASNS ). Downregulation of GLS, GOT2, and ASNS blocked SOX12-mediated CRC cell proliferation and metastasis, whereas ectopic expression of GLS, GOT2, and ASNS attenuated the SOX12 knockdown-induced suppression of CRC progression. In addition, serial deletion, site-directed mutagenesis, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays indicated that hypoxia-inducible factor 1α (HIF-1α) directly binds to the SOX12 promoter and induces SOX12 expression. Administration of l -asparaginase decreased SOX12-mediated tumor growth and metastasis. In human CRC samples, SOX12 expression positively correlated with GLS, GOT2, ASNS, and HIF-1α expression. Based on these results, SOX12 may serve as a prognostic biomarker and l -asparaginase represents a potential novel therapeutic agent for CRC.

The Slit family is a family of secreted proteins that play important roles in various physiologic and pathologic activities via interacting with Robo receptors. Slit/Robo signaling was first identified in the nervous system, where it functions in neuronal axon guidance; nevertheless, an increasing number of studies have shown that Slit/Robo signaling even regulates other activities, such as angiogenesis, inflammatory cell chemotaxis, tumor cell migration and metastasis. Although the precise role of the ligand-receptor in organisms has been obscure and the conclusions drawn are sometimes paradoxical, tremendous advances in understanding the Slit/Robo signaling pathway have been made. As such, our review summarizes the characteristics of the Slit/Robo signaling pathway and its role in various cell types.

Background Multidrug resistance remains a major obstacle to successful treatment for patients with gastric cancer (GC). Recently, glycosylation has been demonstrated to play a vital role in the acquisition of multidrug resistance. As a potent inhibitor of glycosylation, tunicamycin (Tu) has shown marked antitumor activities in various cancers. In the present study, we attempted to determine the exact effect of Tu on the chemoresistance of GC. Methods The cytotoxic effects of drugs on GC cells were evaluated by cell viability assays, and apoptosis was detected by flow cytometry. PCR, western blot analysis, immunofluorescence staining and canonical inhibitors were employed to identify the underlying mechanisms of the specific effects of Tu on multidrug-resistant (MDR) GC cells. Results For the first time, we found that MDR GC cells were more sensitive to Tu-induced cell death than the parental cells and that the increased sensitivity might correlate with basal endoplasmic reticulum (ER) stress. In addition, Tu dramatically increased chemotherapy-induced apoptosis by evoking ER stress in GC cells, particularly MDR cells. Further study indicated that these effects were highly dependent on glycosylation inhibition by Tu, rather than its role as a canonical ER stress inducer. Besides, autophagy was markedly triggered by Tu, and blocking autophagy enhanced the combined effects of Tu and chemotherapy on MDR GC cells. Conclusions Our results suggest that tumor-targeted glycosylation inhibition may be a feasible strategy to reverse chemoresistance in GC patients.